1. Field of the Invention
The invention relates to a device for sterility testing, in particular of pharmaceutical products, comprising a closed sterility test system having at least two test containers, in each case having an integrated test filter, an outlet connecting branch arranged below the test filter and an inlet connecting branch which is arranged above the test filter and can be connected with a tube connection via a sampling device to a sample container. The invention furthermore relates to a method for sterility testing, in particular of pharmaceutical products, in which at least two test containers of a closed sterility test system are filled with an identical sample quantity from a sample container, and the samples are filtered in the test containers, and in which, after an intermediate optional washing process, the test containers are filled with different nutrient media.
2. Description of the Related Art
Regular sterility checks are required for the use of many medicinal and pharmaceutical products. In particular, sterility tests have to be carried out in accordance with the regulations, which are specified in the pharmacopeiae, for using medicines.
In the case of the obligatory membrane filtration method for fluid medicaments—medicaments which are present in solid form may also be first of all dissolved for this using suitable means—two or more identical sample quantities are in each case fed to a test container where they are filtered by a microporous membrane having a pore size of 0.45 μm. The filtrate is then let out of the test containers and the test containers are cleaned using a sterile washing solution possibly from residues which inhibit the growth of germs. The test containers are then filled with different nutrient media, for example with thioglycolate as nutrient medium 1 and with casein soyapeptone as nutrient medium 2, and, with the inlet connecting branch closed, incubated in accordance with the valid pharmacopeiae for example “USP 25” and “EP 4”, at an appropriate temperature for a predefined time, aerobically (with the air filter open) or anaerobically (with the air filter closed). In the event of contamination, a cloud-like opaqueness is formed in the (clear) nutrient fluid.
In order to carry out the sterility test, presterilized disposable sterility test systems which form a system which is closed as far as possible are preferred in order to avoid defective (“falsely positive”) results. Systems of this type are known from EP 0 118 601 A1 and under the designations Steritest™ from Millipore S. A., and Sterisart® from Sartorius Ag. The Sterisart® system, which is known from Sartorius AG's brochure, comprises two transparent, cylindrical test containers with a slightly conical upwards profile which are connected to a sampling device, for example a piercing cannula, by means of a flexible double tube and a Y-distributing component. In the test containers, a respective membrane filter is clamped fixedly in a lower part of the container. The lower part of the container furthermore has a central discharge connecting branch which can be closed with a stopper. The upper part of the container has an inlet connecting branch and a vent having an integrated microporous air filter. The vent can be covered with a rubber cap. The double tube can be fitted into a pump head of a peristaltic hose pump in order to convey samples, washing solutions and nutrient media. Color-coded tube clips are prefitted on the tube connections in order to be able to close and open tube connections according to requirements.
The known sterility test system has been proven in principle. A disadvantage, however, is that it is not optimized in respect of handling with the smallest possible risk of error and in the costs for production and the testing process. In particular, after the filtration process and the washing process, the nutrient media have to be decanted successively via the sampling device into the test containers, or at least two sampling devices to which a respective tube connection to a test container is connected would be required. In order to fill the test containers with the nutrient media, separate nutrient medium containers have to be provided and connected. For this purpose, in the case of a common sampling device, the tube connection has to be connected first of all to the first nutrient medium container, then separated again from the latter and subsequently connected to the second nutrient medium container (in the case of more than two test containers and nutrient media, the process is repeated the appropriate number of times). All these working steps are relatively time-consuming, susceptible to error and conceal the risk of intermediate contamination which may lead to a false positive test result.
It is therefore the object of the present invention to improve the known sterility test system in such a manner that it is associated with a reduced risk of error, and that it is more cost-effective in production and in use.